RU2004538C1 - Способ получени амидов циклометилен-1,2-дикарбоновых кислот - Google Patents
Способ получени амидов циклометилен-1,2-дикарбоновых кислотInfo
- Publication number
- RU2004538C1 RU2004538C1 SU894613962A SU4613962A RU2004538C1 RU 2004538 C1 RU2004538 C1 RU 2004538C1 SU 894613962 A SU894613962 A SU 894613962A SU 4613962 A SU4613962 A SU 4613962A RU 2004538 C1 RU2004538 C1 RU 2004538C1
- Authority
- RU
- Russia
- Prior art keywords
- acid
- mmol
- solution
- oxoethyl
- carbonyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 18
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 239000002253 acid Substances 0.000 claims abstract description 20
- 150000001408 amides Chemical group 0.000 claims abstract description 11
- 125000006239 protecting group Chemical group 0.000 claims abstract description 8
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 238000005984 hydrogenation reaction Methods 0.000 claims abstract description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 3
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 54
- -1 amine derivative of hydroxamic Chemical class 0.000 claims description 25
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 2
- 108020004021 3-ketosteroid receptors Proteins 0.000 abstract 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 44
- 239000013078 crystal Substances 0.000 description 39
- NZNMSOFKMUBTKW-UHFFFAOYSA-N Cyclohexanecarboxylic acid Natural products OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- BFAKENXZKHGIGE-UHFFFAOYSA-N bis(2,3,5,6-tetrafluoro-4-iodophenyl)diazene Chemical compound FC1=C(C(=C(C(=C1F)I)F)F)N=NC1=C(C(=C(C(=C1F)F)I)F)F BFAKENXZKHGIGE-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentane carboxylic acid Natural products OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
- 230000001077 hypotensive effect Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- QKIVRALZQSUWHH-SFYZADRCSA-N (1s,2r)-2-[[2-(hydroxyamino)-2-oxoethyl]-methylcarbamoyl]cyclohexane-1-carboxylic acid Chemical compound ONC(=O)CN(C)C(=O)[C@@H]1CCCC[C@@H]1C(O)=O QKIVRALZQSUWHH-SFYZADRCSA-N 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 3
- 101800000734 Angiotensin-1 Proteins 0.000 description 3
- 102400000344 Angiotensin-1 Human genes 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 3
- 230000003276 anti-hypertensive effect Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 229950010375 idrapril Drugs 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 2
- 229960000830 captopril Drugs 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- MUTGBJKUEZFXGO-UHFFFAOYSA-N hexahydrophthalic anhydride Chemical compound C1CCCC2C(=O)OC(=O)C21 MUTGBJKUEZFXGO-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- MUTGBJKUEZFXGO-WDSKDSINSA-N (3as,7as)-3a,4,5,6,7,7a-hexahydro-2-benzofuran-1,3-dione Chemical compound C1CCC[C@@H]2C(=O)OC(=O)[C@H]21 MUTGBJKUEZFXGO-WDSKDSINSA-N 0.000 description 1
- CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- GLJPYGONZAPOSG-UHFFFAOYSA-N aminomethyl acetate Chemical compound CC(=O)OCN GLJPYGONZAPOSG-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 208000037849 arterial hypertension Diseases 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- KSDIHKMNSYWRFB-UHFFFAOYSA-N chrysen-2-amine Chemical compound C1=CC=CC2=CC=C3C4=CC=C(N)C=C4C=CC3=C21 KSDIHKMNSYWRFB-UHFFFAOYSA-N 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- ZQWPRMPSCMSAJU-UHFFFAOYSA-N cyclohexanecarboxylic acid methyl ester Natural products COC(=O)C1CCCCC1 ZQWPRMPSCMSAJU-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- NRMPJIHWGVBZBB-UHFFFAOYSA-N ethyl 2-(ethylamino)acetate Chemical compound CCNCC(=O)OCC NRMPJIHWGVBZBB-UHFFFAOYSA-N 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 108010023700 galanin-(1-13)-bradykinin-(2-9)-amide Proteins 0.000 description 1
- 229940043257 glycylglycine Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- RGZRSLKIOCHTSI-UHFFFAOYSA-N hydron;n-methylhydroxylamine;chloride Chemical compound Cl.CNO RGZRSLKIOCHTSI-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- NZDJTVSTIFYISQ-UHFFFAOYSA-N iodomethyl acetate Chemical compound CC(=O)OCI NZDJTVSTIFYISQ-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000012886 linear function Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QOEALULCQUCMOP-UHFFFAOYSA-N methyl 2-(aminomethyl)-3-phenylpropanoate Chemical compound COC(=O)C(CN)CC1=CC=CC=C1 QOEALULCQUCMOP-UHFFFAOYSA-N 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/61—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Eyeglasses (AREA)
- Polyamides (AREA)
- Non-Silver Salt Photosensitive Materials And Non-Silver Salt Photography (AREA)
- Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT8820172A IT1224627B (it) | 1988-04-12 | 1988-04-12 | Ammidi di acidi ciclometilen_1,2_dicarbossilici adattivita' terapeutica, procedimenti per la loro preparazione e composizioni farmaceutiche che le contengono. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2004538C1 true RU2004538C1 (ru) | 1993-12-15 |
Family
ID=11164400
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU894613962A RU2004538C1 (ru) | 1988-04-12 | 1989-04-11 | Способ получени амидов циклометилен-1,2-дикарбоновых кислот |
| SU894614855A RU1838294C (ru) | 1988-04-12 | 1989-08-28 | Амиды циклометилен-1,2-дикарбоновых кислот, обладающие гипотензивной активностью |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU894614855A RU1838294C (ru) | 1988-04-12 | 1989-08-28 | Амиды циклометилен-1,2-дикарбоновых кислот, обладающие гипотензивной активностью |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US5095137A (it) |
| EP (1) | EP0337348B1 (it) |
| JP (1) | JPH026452A (it) |
| KR (1) | KR900016097A (it) |
| CN (1) | CN1037344A (it) |
| AT (1) | ATE101126T1 (it) |
| AU (1) | AU611796B2 (it) |
| BG (1) | BG60556B1 (it) |
| CA (1) | CA1314903C (it) |
| DD (1) | DD294014A5 (it) |
| DE (1) | DE68912811T2 (it) |
| DK (1) | DK173689A (it) |
| ES (1) | ES2061759T3 (it) |
| FI (1) | FI891712A (it) |
| HU (1) | HU206194B (it) |
| IL (1) | IL89895A0 (it) |
| IN (2) | IN169836B (it) |
| IT (1) | IT1224627B (it) |
| MX (1) | MX15635A (it) |
| NO (1) | NO177851C (it) |
| NZ (1) | NZ228688A (it) |
| PL (1) | PL159413B1 (it) |
| PT (1) | PT90254B (it) |
| RO (1) | RO104347B1 (it) |
| RU (2) | RU2004538C1 (it) |
| UA (1) | UA15920A (it) |
| YU (1) | YU73889A (it) |
| ZA (1) | ZA892674B (it) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1252708B (it) * | 1991-12-23 | 1995-06-26 | Guidotti & C Spa Labor | Sali stabili dell'acido (+)-(1r,2s)-2((n-(2-idrossilammino-2-ossoetil)-n-metilammino)carbonil)cicloesan-1-carbossilico,ad attivita' ace inibitrice, procedimento per la loro preparazione e composizioni farmaceutiche che li contengono. |
| US5977160A (en) * | 1992-04-10 | 1999-11-02 | Brigham And Women's Hospital, Inc. | Methods for reducing risk of repeat myocardial infarction and increasing survival in heart attack victims |
| IT1264860B1 (it) * | 1993-06-21 | 1996-10-17 | Guidotti & C Spa Labor | Derivati di acidi cis- e trans-2(((2-(isdrossiammino)-2-ossoetil)- alchilammino)carbonil)cicloesancarbossilici |
| US5639746A (en) * | 1994-12-29 | 1997-06-17 | The Procter & Gamble Company | Hydroxamic acid-containing inhibitors of matrix metalloproteases |
| US6028213A (en) * | 1998-04-16 | 2000-02-22 | Eastman Chemical Company | Optically active cis-1,3-cyclohexanedicarboxylic acid monoesters with high enantiomeric purity and process for their preparation |
| WO2008012524A1 (en) * | 2006-07-24 | 2008-01-31 | Ucb Pharma S.A. | Substituted aniline derivatives |
| US20100168243A1 (en) * | 2007-06-20 | 2010-07-01 | Baldwin John J | Renin Inhibitors |
| WO2008156816A2 (en) | 2007-06-20 | 2008-12-24 | Vitae Pharmaceuticals, Inc. | Renin inhibitors |
| BRPI0907612A2 (pt) | 2008-01-08 | 2015-07-21 | Lantheus Medical Imaging Inc | Conjugados de n-coxiamida como agentes de imageamento |
| US8877157B2 (en) | 2009-07-08 | 2014-11-04 | Lantheus Medical Imaging, Inc. | N-alkoxyamide conjugates as imaging agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4077998A (en) * | 1975-10-28 | 1978-03-07 | Morton-Norwich Products, Inc. | Phthaloyl amino acid hydroxamic acids |
| US4687841A (en) * | 1985-10-18 | 1987-08-18 | Monsanto Company | Peptide hydroxamic acid derivatives |
-
1988
- 1988-04-12 IT IT8820172A patent/IT1224627B/it active
-
1989
- 1989-04-10 IL IL89895A patent/IL89895A0/xx not_active IP Right Cessation
- 1989-04-10 DE DE68912811T patent/DE68912811T2/de not_active Expired - Fee Related
- 1989-04-10 AT AT89106304T patent/ATE101126T1/de not_active IP Right Cessation
- 1989-04-10 ES ES89106304T patent/ES2061759T3/es not_active Expired - Lifetime
- 1989-04-10 EP EP89106304A patent/EP0337348B1/en not_active Expired - Lifetime
- 1989-04-11 PT PT90254A patent/PT90254B/pt not_active IP Right Cessation
- 1989-04-11 UA UA4614855A patent/UA15920A/uk unknown
- 1989-04-11 RU SU894613962A patent/RU2004538C1/ru active
- 1989-04-11 FI FI891712A patent/FI891712A/fi not_active Application Discontinuation
- 1989-04-11 DK DK173689A patent/DK173689A/da not_active IP Right Cessation
- 1989-04-11 NO NO891484A patent/NO177851C/no unknown
- 1989-04-11 HU HU891735A patent/HU206194B/hu not_active IP Right Cessation
- 1989-04-11 CA CA000596331A patent/CA1314903C/en not_active Expired - Fee Related
- 1989-04-11 NZ NZ228688A patent/NZ228688A/en unknown
- 1989-04-12 ZA ZA892674A patent/ZA892674B/xx unknown
- 1989-04-12 KR KR1019890004818A patent/KR900016097A/ko not_active Application Discontinuation
- 1989-04-12 YU YU00738/89A patent/YU73889A/xx unknown
- 1989-04-12 PL PL1989278804A patent/PL159413B1/pl unknown
- 1989-04-12 RO RO139231A patent/RO104347B1/ro unknown
- 1989-04-12 DD DD89327552A patent/DD294014A5/de not_active IP Right Cessation
- 1989-04-12 IN IN283/CAL/89A patent/IN169836B/en unknown
- 1989-04-12 BG BG88028A patent/BG60556B1/bg unknown
- 1989-04-12 CN CN89102213A patent/CN1037344A/zh active Pending
- 1989-04-12 JP JP1092774A patent/JPH026452A/ja active Pending
- 1989-04-12 AU AU32655/89A patent/AU611796B2/en not_active Ceased
- 1989-04-12 MX MX1563589A patent/MX15635A/es unknown
- 1989-08-28 RU SU894614855A patent/RU1838294C/ru active
-
1990
- 1990-10-09 US US07/595,639 patent/US5095137A/en not_active Expired - Fee Related
- 1990-11-29 IN IN1000/CAL/90A patent/IN172059B/en unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU639706B2 (en) | Hydroxamic acid based collagenase inhibitors | |
| US4052511A (en) | Carboxyacylproline derivatives | |
| US4297346A (en) | Pseudopeptides used as medicaments | |
| BG60936B2 (bg) | Нови производни на бициклични аминокиселини,методи за тяхното получаване,средства,които ги съдържат и тяхното приложение,както и нови бициклични аминокиселини като междинни продукти и методи за тяхно то получаване | |
| FR2701480A1 (fr) | Composés à groupe sulfamoyle et amidino, leur procédé de préparation et les compositions pharmaceutiques les contenant. | |
| JPH0437070B2 (it) | ||
| RU2004538C1 (ru) | Способ получени амидов циклометилен-1,2-дикарбоновых кислот | |
| EP0116276B1 (de) | Neue spirocyclische Aminosäurederivate, Verfahren zu ihrer Herstellung, diese enthaltende Mittel und deren Verwendung sowie neue spirocyclische Aminosäuren als Zwischenprodukte und Verfahren zu deren Herstellung | |
| US4154937A (en) | Hydroxycarbamoylalkylacylpipecolic acid compounds | |
| EP0190891A2 (en) | Novel amino acid derivatives | |
| WO2000017158A1 (de) | Urokinase-inhibitoren | |
| DE4443390A1 (de) | Neue dipeptidische p-Amidinobenzylamide mit N-terminalen Sulfonyl- bzw. Aminosulfonylresten | |
| US5886046A (en) | Dicarbonyl-containing compounds | |
| US4134991A (en) | Derivatives of 2-(3-phenyl-2-aminopropionyloxy)-acetic acid | |
| JPH04230358A (ja) | α−メルカプトアルキルアミンの新規なＮ−置換誘導体、それらの製造法及び中間体、それらの薬剤としての使用並びにそれらを含有する組成物 | |
| JPS6383053A (ja) | 環状脂肪族アルコールのアミノ酸エステル類、その製法と医薬組成物 | |
| US4500713A (en) | Therapeutic dipeptides | |
| US5068242A (en) | Pyrrolidine-2-carboxylic acid derivatives and their use for psychotropic action | |
| CH689611A5 (de) | Urokinase-Inhibitoren. | |
| JPH0517439A (ja) | 光学的に活性な二環式イミノ−α−カルボン酸エステルのラセミ体の分割法で得られた化合物 | |
| EP0053017A1 (en) | Amide derivatives | |
| US4563477A (en) | Process for the preparation of alpha-(N-pyrrolyl)-derivative acids, the salts and esters thereof; alpha-(N-pyrrolyl)-phenylacetic acids, the esters thereof, pharmaceutical compositions containing them and therapeutical applications thereof | |
| NO832601L (no) | Fremgangsmaate for fremstilling av et amid-derivat | |
| DE69226443T2 (de) | N-(mercaptoacyl)aminosäure, ihre herstellung, ihre therapeutische verwendung und sie enthaltende pharmazeutische zusammensetzungen | |
| NO883818L (no) | Nye forbindelser. |